Fungal ergosterol biosynthesis pathway

The **fungal ergosterol biosynthesis pathway** is a multi-step metabolic process responsible for producing ergosterol, the principal sterol component unique to fungal cell membranes. This molecule is essential for maintaining membrane structure, fluidity, permeability, and various cellular processes critical for fungal viability and pathogenicity. The pathway involves approximately 20 enzymatic steps converting squalene into ergosterol through intermediates such as lanosterol. Key enzymes include lanosterol 14α-demethylase (CYP51/ERG11), which is targeted by azole antifungals. Because **ergosterol** is not found in animal cells—where cholesterol serves an analogous role—the enzymes involved in its synthesis are highly selective targets for antifungal drugs. Major classes targeting this route include azoles (inhibiting CYP51), polyenes (binding directly to ergosterol), allylamines, and morpholine derivatives. However, widespread use has led to increasing drug resistance among pathogenic fungi due to genetic adaptations like overexpression or mutation of target genes. Disruption or inhibition of this biosynthetic route impairs cell membrane integrity and function—ultimately inhibiting growth or causing death in susceptible fungi—making it a cornerstone therapeutic target against invasive mycoses.[1][3][5]

Other names

Ergosterol synthesis pathwayErgosterol biosynthetic pathwayFungal sterol biosynthesisErgosterol pathway

Inhibition of key enzymes in the ergosterol biosynthetic pathway, primarily lanosterol 14α-demethylase by azoles, leading to depletion of ergosterol and accumulation of toxic sterols that disrupt membrane function[5][6].